, AND TOMIO TADA 445 Preparation of Th - 1 and Th - 2 Specific for KLH

A number of recent reports indicate the existence of more than one type of helper T cell (I-6). A previous publication from our laboratory (3) demonstrated two types of carrier-specific helper T cells that independently and synergistically exert helper effects on the hapten-specific antibody response. One type (Thl) 1 is a more conventional helper T cell that helps hapten-specific B cells only in the presence of the relevant hapten-carrier conjugate (cognate help), whereas the other (Th2) can help B cells stimulated with hapten on a different carrier (polyclonal help). A notable difference is that Th2 possesses determinants coded for by a gene in I-J subregion of H-2 major histocompatibility complex, whereas Thx has not detectable Ia antigens. Both belonged to the Lyt-1 +, 2-, 3subset. Similar findings have been reported by others using different experimental systems (4, 5). Another criterion for distinguishing different types of helper T cells is whether their helper effect is restricted to B cells expressing certain allotypes and idiotypes (7-11). It has been noted (7) that allotype-specific suppressor T cells (Ts) inhibit the production of one allotype but not the other in F1 animals through the neutralization of helper T cells. Because production of the second allotype is unaffected, it was presumed that there exists a helper T cell population recognizing allotype-related structures on B cells. Two kinds of helper cells, one being a conventional antigenspecific helper T cell and the other recognizing immunoglobulin (Ig) structures on responding B cells, were reported by Janeway et al. (2, 12-14). These two helper subsets act synergistically to promote a higher antibody response than either one alone. In addition, recent studies by many investigators demonstrate a specialized T cell population that preferentially help idiotype-positive responses (5, 8, 10, 11). To determine whether our Th~ or Th2 are identical to the Ig-restricted helper T cell reported by other systems (7), we co-cultured B cells and Thl or Th2 derived from Ig congenic strains and measured antibody production. No Ig restriction between B cells and either type of helper T cells was detected (K. Okumura et al., unpublished observation). Thus, we set up a series of experiments to identify Ig-restricted helper T cells. By the addition of different fractionated cells into cultures of B cells with limited l Abbreviations used in this paper: Ars, arsonic acid; B', Thy-l-, Lyt-I +, Ig ÷ nylon-adherent cells; BAT, brain-associated T cell antigen; BSA, bovine serum albumin; C, complement; DNP, 2,4-dinitrophenyl; FCS, fetal calf serum; KLH, keyhole limpet hemocyanin; MEM, Eagle's minimal essential medium; MIg, mouse immunoglohulin; The, nylon-nonadherent helper T cells; Th2, nylon-adherent helper T cells.