CD11B(-)CD4(+) HUMAN T-CELLS - ACTIVATION REQUIREMENTS AND ASSOCIATION WITH HLA-DR ALLELES()CD28()

Engagement of CD28 induces a major costimulatory pathway required by m any CD4(+) T cells in addition to activation via the TCR, In the absen ce of signals provided by CD28, ligation of the TCR alone can induce a nergy or apoptosis in CD28(+) cells, However, we report here character ization of a distinct subset of CD4(+) T cells that are CD28(-). Three autoreactive CD4(+) human T cell clones that could be activated to pr oduce IL-2 and proliferate by anti-CD3 alone were found to lack expres sion of CD28, CD28(-) clones that were activated with anti-CD3 alone w ere not anergic to restimulation via CD3, The presence of CD28(-)CD4() T cells was verified in peripheral blood, and their frequency ranged from 0% to > 22% of CD4(+) T cells in different individuals, The perc entage of CD28(-)CD4(+) T cells in the peripheral blood of 57 individu als was significantly correlated with specific class II MHC alleles, P ersons with HLA-DRB10401 and DR1 alleles had significantly higher num bers of CD28(-) T cells, while individuals with HLA-DR2(15) had signif icantly fewer CD28(-)CD4(+) T cells than the mean, Like the CD28(-) cl ones, CD28(-)CD4(+) T cells isolated from peripheral blood proliferate d upon CD3 cross-linking in the absence of costimulation, The finding that CD28(-)CD4(+) T cells resist induction of anergy following engage ment of the TCR in the absence of conventional costimulation demonstra tes one mechanism by which autoreactive T cells can escape processes t hat censor self-reactivity, The MHC associations observed suggest a re lationship with autoimmunity and loss of self-tolerance.