Dependence of lymphopenia-induced T cell proliferation on the abundance of peptide/ MHC epitopes and strength of their interaction with T cell receptors

Abstract

Factors that affect naïve T cell proliferation in syngeneic lymphopenic hosts were investigated. 2C T cell receptor (TCR) transgenic T cells lacking both CD8 and CD4 survived but hardly proliferated. Proliferation of CD8 ؉ 2C cells was proportional to the abundance of cognate peptide͞MHC complexes and was severely inhibited by injection of anti-CD8 antibody. Weakly reactive selfpeptides slightly enhanced CD8 ؉ 2C cell proliferation whereas a potent agonist peptide promoted much more rapid proliferation, but inflammation-stimulating adjuvant had only a small effect on the rate of cell proliferation. The findings suggest that under uniform lymphopenic conditions, the widely different rates of proliferation of T cells expressing various TCR, or the same TCR in the presence or absence of CD8, reflect the strength of interaction between TCR and MHC associated with particular self-peptides.

γδ T Cell Homeostasis Is Controlled by IL-7 and IL-15 Together with Subset-Specific Factors

“…However, it is also possible that episodes of lymphopenia targeting subpopulations of cells in defined tissues are common during normal life, as a result of exposure to infectious agents, cytotoxic compounds, radiation or apoptosis-inducing signals. Considering that, during homeostatic expansion, T cell clonotypes with increased affinity for highly represented ligands have a selective advantage (32)(33)(34) and acquire a preactivated phenotype (9), it is conceivable that homeostatic proliferation is a mechanism that evolved, in part, to allow a rapid resetting of the lymphocyte repertoire for faster and more efficient immune responses. In support of this possibility, we (35) and others (36,37) have shown that homeostatic expansion concurrent with immunization generates T cell populations enriched for CD8 ϩ effectors with enhanced antitumor activities.…”

T cell homeostasis and systemic autoimmunity

“…The reasons for this selective response remain unclear, but it may be that some positiveselecting peptides are absent from the periphery or that expansion is restricted to cells with higher selfaffinity. Recent experiments with transgenic T cells favor the second possibility (27). The relevance of homeostatic anti-self proliferation of naive T cells to autoimmunity rests to a great extent on whether the proliferating cells acquire effector function and differentiate to the activated/memory phenotype.…”

“…The relevance of homeostatic anti-self proliferation of naive T cells to autoimmunity rests to a great extent on whether the proliferating cells acquire effector function and differentiate to the activated/memory phenotype. Several studies in which TCR transgenic CD8 + or CD4 + cells were transfused to lymphopenic syngeneic hosts appear to provide an affirmative answer (11,(25)(26)(27)(28)(29). Proliferating TCR transgenic CD8 + cells kill target cells ex vivo in a peptide-and TCRdependent manner, and express IFN-γ after stimulation with anti-CD3.…”

The Death Receptor Fas (CD95/APO-1) Mediates the Deletion of T Lymphocytes Undergoing Homeostatic Proliferation

“…Experimental studies of homeostatic proliferation in lymphopenic recipients revealed that the transferred lymphocytes from a single donor inoculum do not completely restore the T cell compartment (13)(14)(15)(16)(17). Although the number of T cells recovered increases, a plateau is reached at ϳ4 wk.…”