Disease relevance of Cd4

• Role of L3T4 antigen in the activation of various functions of Lyt-1+2- T cells against vaccinia virus [1].
• A subset of T cell receptors associated with L3T4 molecules mediates C6VL leukemia cell binding of its cognate retrovirus [2].
• To address this issue, we have studied alpha/beta T-cell antigen receptor gene and protein expression on normal thymocyte subsets of AKR/J mice, as well as on a panel of AKR/J primary thymic lymphomas characterized for CD4 (L3T4) and CD8 (Lyt-2) differentiation antigen expression [3].
• Protection was determined by comparing the number of viable splenic Listeria in naive mice and in recipients of 60 million CD8-enriched, L3T4-depleted, Listeria-immune spleen cells, 2 days after the infusion of 10,000 Listeria [4].
• In contrast, PGF did not ameliorate splenomegaly, but caused increases in splenic asialo-GM1 (natural killer cells) and L3T4 (helper) positive T cells [5].

High impact information on Cd4

• While an anti-clonotypic antibody completely inhibits this interaction, antibodies specific for another T cell receptor complex determinant, L3T4, only partially inhibit the cell-retrovirus interaction [2].
• The other population expresses low levels of Thy-1, and lacks B220 as well as the T cell markers L3T4 and Lyt-2 [6].
• Engagement of SLAM enhances antigen-specific proliferation and cytokine production by T cells carrying the CD4 antigen (CD4+) [7].
• The virus enters cells by binding its envelope glycoprotein gp120 to the CD4 antigen present on brain and immune cells [8].
• Thymocytes can be divided into four major compartments on the basis of surface expression of the murine equivalents of CD8 (Lyt-2) and CD4 (L3T4) (refs 1,2) [9].

Chemical compound and disease context of Cd4

• In vivo therapy with monoclonal antibody (mAb) GK1.5, which recognizes a glycoprotein antigen designated L3T4 on murine helper T lymphocytes, either prevented or suppressed the development of murine lupus, autoimmune encephalomyelitis, and collagen arthritis [10].
• These T-cell lines, consisting mainly of L3T4 surface antigen-positive cells, were transferred intravenously into nude mice infected with M. bovis strain bacillus Calmette-Guérin (BCG) [11].

Biological context of Cd4

• L3T4 is one such T-cell surface protein that is expressed on most mouse thymocytes and on mature mouse T cells that recognize class II (Ia) major histocompatibility complex proteins [12].
• The predicted protein sequence shows that L3T4 is a member of the immunoglobulin gene superfamily [12].
• In the present study the gene encoding L3T4 is shown to span 26 kilobases and to contain 10 exons [13].
• The gene encoding the mouse T cell differentiation antigen L3T4 is located on chromosome 6 [14].
• Four features of accessory cell function were explored: antigen processing, interaction with accessory molecules (LFA-1, L3T4), influence of Ia density, and ability to stimulate resting, unprimed T lymphocytes [15].

Anatomical context of Cd4

• Single-cell RT-PCR showed that the individual CD4+ lymphocyte expresses either the maternal or the paternal Cd4 allele, never both [16].
• In addition, a small subpopulation comprising 2-3% of cells in the thymus and expressing neither Lyt-2 nor L3T4 has recently been described [17].
• The minor species comigrates with the L3T4 transcript in T cells, whereas the major species is 1 kilobase smaller [12].
• We show here for the first time that pluripotent hematopoietic stem cells express the CD4 antigen [18].
• The phenotypically comparable Lyt-2- L3T4- subset of normal thymocytes expressed approximately 10-fold less TCR-alpha mRNA than normal lymph node cells and somewhat higher TCR-beta mRNA [19].

Associations of Cd4 with chemical compounds

• The level of expression of the function-associated antigens CD4 (L3T4) and CD8 (Ly-2) decreased transiently early after activation with PMA/ionomycin, but not after stimulation with Con-A [20].
• Surface marker analysis indicated that majority of effector cells which killed syngeneic lymphoblasts and activated M phi were Thy1+, asialo GM1+, L3T4-, Ly2- [21].
• In vitro proliferation of murine spleen cells: inhibition by monoclonal antibodies to L3T4 and Lyt-2 T cell markers or intracellular cyclic adenosine monophosphate [22].
• These populations of T cells could be distinguished in that they differed in their expression of the L3T4 and Lyt-2 cell surface molecules, in terms of their kinetic profiles of emergence and loss, and (c) in terms of their susceptibility to cyclophosphamide [23].
• We have studied the effects of the steroid hormones, 17 beta-estradiol and dexamethasone, on the relative proportion of thymocyte expression of CD4 (L3T4), CD8 (Ly-2), TCR and IL-2R, used to identify different stages of thymocyte differentiation [24].

Physical interactions of Cd4

• The expression of L3T4/Lyt-2 on murine T cells has led to the association of these surface markers with recognition of either class II or class I major histo-compatibility complex (MHC) antigens [25].
• The currently accepted hypothesis used to explain the role of Lyt-2 and L3T4 in T cell activation proposes how these molecules interact with class I and II major histocompatibility complex molecules, respectively, on the antigen-presenting or target cell, to increase the avidity of binding of the antigen-specific T cell receptor [26].

Regulatory relationships of Cd4

• The poor blocking observed with L3T4 mAb did not correlate with the almost complete blocking observed in the IL 2 response by the same hybridomas [27].

Other interactions of Cd4

• Interferon-gamma-positive, L3T4-positive cells were detected in mirror sections [28].
• With the use of a depletion method based on complement-mediated lysis with an anti-Lyt-2 monoclonal antibody (31 M) and a new anti-L3T4 monoclonal antibody (RL 172.4), we have purified the Lyt-2- L3T4- subset from lymph nodes or spleens of C57BL/6-lpr/lpr mice and determined whether they are immunologically functional in vitro [29].
• In the case of stimulation with accessory cell-bound CD3 antibody, activation was blocked by LFA-1 but not L3T4 antibody [30].
• The expression of L3T4 was also reduced in some of the experiments, while IL-2R was not expressed by the thymocytes, neither before nor after the co-culture [31].
• Although Thy-1+ they were negative for other differentiation antigens including Ly-1, Ly-2 and L3T4 [32].

Analytical, diagnostic and therapeutic context of Cd4

• In situ hybridization proved that Cd4 alleles replicate asynchronously, as expected in the case of genes expressed monoallelically [16].
• However, phenotypic analysis by using flow microfluorometry and monoclonal antibodies to Lyt-2 and L3T4 showed little differentiation among proliferating 2-4-fetal thymocytes [33].
• We have used Southern blot analysis of DNA from somatic cell hybrids to map the chromosomal location of the mouse L3T4 T cell differentiation antigen gene to chromosome 6 [14].
• Electron immunohistochemistry by immunogold technique showed that effector cells in IAMCs reacted with anti-CD8 (Lyt-2) antibody, but not anti-CD4 (L3T4) or anti-asialogangliosideM1 antibody [34].
• Monoclonal antibody GK1.5 recognizes a previously undescribed murine T cell surface molecule, designated L3T4, which migrates on SDS-PAGE under reducing conditions as a single band with an apparent m.w. of 52,000 [35].

References