# Chemokine mediated lymphocyte migration

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $192,500

## Abstract

RPOJECT SUMMARY/ABSTRACT
Adoptive cell transfer (ACT) of in vitro activated T cells into the recipient animals has been widely used to study
the dynamics of T cell migration and differentiation and the process of effector functions in several disease
models including acute/chronic inflammation, autoimmune disease, and graft rejection. Clinically, ACT has
emerged as a promising therapeutic approach with complete and durable responses in several infectious and
malignant diseases. For example, ACT utilizing genetically engineered cytotoxic T lymphocytes (CTLs) (e.g.,
chimeric antigen receptor (CAR)-T cells) has proven effective in treating many types of cancer. However, early
studies on the fate of activated cloned CD8+ T cells after intravenous transfer into normal recipient mice
indicated that these differentiated effector T cells are primarily retained in the non-inflamed tissues for a
prolonged period before they become available in the blood for the subsequent migration into inflamed tissues.
We demonstrated that the migration and retention of adoptively transferred activated effector CD8 T cells in the
lung microcirculation is mediated by integrin LFA-1 (lymphocyte function-associated antigen-1 or αLβ2;
CD11a/CD18), while it is insensitive to pertussis toxin (PTx). Spontaneous/chemokine-independent migration
of in vitro activated CD8 T cells is closely associated with the dramatic down-regulation of an LFA-1-associated
cytoskeletal protein, βII-spectrin, and distinct endosomal redistribution patterns of LFA-1 in activated CD8 T
cells. We hypothesize that CD8 T cells acquire key cell intrinsic cues during strong in vitro activation,
which allows chemokine-independent LFA-1 activation and T cell migration into non-inflamed tissue
sites upon intravenous transfer. We will, (1) determine the molecular mechanisms for chemokine-
independent migration of activated CD8 T cells and (2) test whether we can generate T cells with an improved
tissue-specific homing property. The molecular and cellular characterization of chemokine-independent,
spontaneous migration of highly activated CD8 T cells will open up new therapeutic possibilities for
inflammatory diseases. The effectiveness of clinical approaches using ACT may be specifically enhanced by
our discovery of important mediators that can improve (chemokine-dependent) tissue-specific migration of
adoptively transferred T cells while minimizing the (chemokine-independent) sequestration at non-inflamed
tissues.

## Key facts

- **NIH application ID:** 9822155
- **Project number:** 5R21AI143182-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Minsoo Kim
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2018-11-15 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822155

## Citation

> US National Institutes of Health, RePORTER application 9822155, Chemokine mediated lymphocyte migration (5R21AI143182-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9822155. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*